Project Summary. Dr. Weaver seeks this K25 mentored training award to expand her bioengineering research background in medical imaging and finite element modeling of trauma towards pursuit of an independent research career focused on reducing osteoporosis and fracture in older adults. Weight loss poses an increased risk of bone loss and fracture in older adults. The proposed research will test the overall hypothesis that higher dietary protein intake during and following weight loss will attenuate bone loss in older adults with obesity. Guided by an accomplished multidisciplinary mentoring team with expertise in aging, clinical trials, bone metabolism, nutrition, and radiology, the PI will: (1) Develop knowledge of gerontology and geriatric medicine, (2) Acquire training in the design and execution of clinical trials, 3) Obtain in-depth knowledge on bone metabolism and structure, including the influence of nutrition and weight loss, and 4) Develop expertise in dual-energy computed tomography (CT) acquisition and post-processing to measure volumetric bone mineral density, cortical thickness, and bone marrow adipose tissue. Dr. Weaver's training and research will take place at Wake Forest School of Medicine which has a strong history of clinical research in aging and an exceptional radiology infrastructure. The partnership with her co-mentor at Rutgers within the Department of Nutritional Sciences will provide additional resources and expertise related to the nutritional regulation of bone metabolism. The proposed ancillary study to the ongoing clinical trial, UPLIFT: Utilizing Protein During Weight Loss to Impact Physical Function, will examine bone health over 6 months of active weight loss, followed by 12 months of weight maintenance. Musculoskeletal phenotypes will be compared in older adults with obesity randomized to either: (1) a lower protein diet for weight loss and follow-up, (2) a higher protein diet for weight loss only, or (3) a higher protein diet for weight loss and follow-up. The ancillary study expands the UPLIFT trial by adding dual-energy CT scans of the lumbar spine and proximal femur at baseline, 6 months, and 18 months to compare the influence of a higher versus lower protein intake on: vertebral and femoral trabecular volumetric bone mineral density and cortical thickness (Primary Aim), bone marrow adiposity which may alter the trabecular matrix and affect bone strength (Secondary Aim 1), and bone strength and fracture risk predicted with subject-specific finite element modeling (Secondary Aim 2). The study will test if a higher protein diet improves bone outcomes during active weight loss (evaluated at 6 months), and if maintaining higher protein intake during weight maintenance further preserves bone (evaluated at 18 months). The proposed training and research plan will launch Dr. Weaver's career as an independent investigator focused on applying bioengineering techniques to: 1) develop translational tools for fracture prediction, and 2) assess osteoprotective interventions in clinical trials?ultimately leading to improved diagnostics, prognostic tools, clinical recommendations, and therapies for preventing osteoporosis and fracture in older adults.